Researchers massively edit the genome of pigs to turn them into perfect human organ donors

October 8, 2015 by John Hewitt report
Researchers massively edit the genome of pigs to turn them into perfect human organ donors
CRISPR gene editing of the pig genome. Credit: Editors-in-Chief Franco J. DeMayo and Thomas Spencer, Biology of Reproduction

(Phys.org)—One benefit of the closeness between pigs and humans is the potential to be organ donors. There are however, just a few nagging uncertainties that still stand in the way. The big one, the possibility of porcine endogenous retroviruses (PERVs) getting reactivated inside the human organ recipient, is no longer the concern it once was. That comes thanks to the recent groundbreaking work of the one-man army of genetics, George Church, and his lab at Harvard. The latest news, just reported in Nature, is that the group was able to use CRISPR gene-editing techniques to inactivate 62 PERVs in pig embryos.

The one other big concern is rejection of donor organs by the human immune system. Church has reportedly tackled that problem too, by modifying over 20 genes in additional embryos that make the proteins that irritate our immune cells. Although many of these proteins typically reside on the cell surface, they can also be interior proteins which ultimately get chopped up into representative 'tags' that are exposed at the surface. We don't yet know exactly which genes these all are (and they will hopefully soon be published), but one might be able to make a few good guesses.

Researchers in China, have also had recent successes in making multiple CRISPR edits to pig genomes. They were even able to combine the technique with somatic cell nuclear transfer (the method used correct various mutations in the creation of multi-parental embryos) without mosaic mutation or any of the usual undesirable 'off-target' effects. Perhaps the most arresting news from the Chinese pig geneticists has been their creation of custom pet rainbow micropigs. Not only are these pigs miniature due to inactivation of one copy of their gene, but they can be ordered in different colors.

Clearly the genomes of all the higher forms of multicellular life must be no strangers to retroviruses. Not only did these genetic inserts co-evolve with their hosts, they orchestrated many of the primary genetic rearrangements that drove key physiologic adaptations—signature innovations like, for example, placentas. Primate genomes are littered with over a million copies one particular class of repeat elements that are believed to be retroviral derivatives. These elements, known as Alu's, seem to have evolved from various signal recognition RNAs, and possibly a few transfer RNAs.

What is particularly interesting here, is that it was recently shown that pigs devote roughly the same percentage of their genome as primates (about 11%) to a repeat that is almost the same as the Alu's. These porcine repeat elements (known as PRE-1) are structurally and functionally very similar to the primate Alu's and as the authors report, hint at a much closer relationship between us and swine than had former been appreciated.

It has been shown some time ago that human receptors for pig PERVs exist. However if PERVs can just be genetically inactivated, then we don't have to worry too much about trying to make vaccines against them. At this point in the game it is probably important to be sure not only that all the important PERVs have been inactivated, but that their loss doesn't compromise the animal. We might note that despite the clear benefits, making just a single alteration to create genetically-modified plants can still affect their fitness at some level. There probably won't be cataclismic unintended consequences to the environment, or even to the modified organism, but a little caution won't hurt. In every sense of the word, these pigs are GMO's.

Church, and his startup company eGenesis, hope to begin implanting gene-edited pig embryos into mother pigs as soon as it is possible. For an animal that is so close to humans to at once serve not just as food and pet, but also as a organ backup—and do all at once—should give some pause for concern. If the gene editors can also give the pig vocal chords, they might then be able negotiate a deal to serve in the latter two capacities, but perhaps forgo the former.

Explore further: The hidden evolutionary relationship between pigs and primates revealed by genome-wide study of transposable elements

More information: Gene-editing record smashed in pigs, Nature DOI: 10.1038/nature.2015.18525 , http://www.nature.com/news/gene-editing-record-smashed-in-pigs-1.18525

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18 comments

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ScottyB
5 / 5 (2) Oct 08, 2015
Oh pigley
rgw
3.9 / 5 (7) Oct 08, 2015
Love to be a fly on the wall at a Saudi prince's organ replacement evaluation.
crusher
3.7 / 5 (3) Oct 08, 2015
there are lot of minor histocompatibility antigens that have to remove also.
dogbert
3 / 5 (6) Oct 08, 2015
I am always disturbed by the alacrity with which we mix human and animal tissues. There is great danger that an animal pathogen will develop the capacity to infect humans when tissues, particularly living tissues, are mixed.

Consider H.I.V., which was a simian virus that developed the capacity to infect humans when the pathway was only that humans were eating monkeys and apes.

We could easily develop another world wide epidemic from missing human and animal tissues.

thomas_s_dunn
3.7 / 5 (3) Oct 08, 2015
Big man, pig man ha ha charade you are.
cgsperling
4.2 / 5 (5) Oct 08, 2015
Jeebus, the double entendres are all over this. Church starts eGenesis to eliminate the PERVs. CRISPR is used to edit the bacon. LOL.
someone11235813
3 / 5 (2) Oct 08, 2015
Big man, pig man ha ha charade you are.


One day soon they'll be flying. Pigs on the wing.
theyfly_com
3 / 5 (2) Oct 08, 2015
Take
Here
Everyone
Your
Flowers
Lovely
Yes?
.
Consentrate
On
Marigold
jimbo92107
4 / 5 (4) Oct 09, 2015
Sizzling article, crackling humor. Best use of bacon in a science graphic.
Lex Talonis
3 / 5 (2) Oct 09, 2015
MMmmmmmmm Awesome.

FOOD PORN

Google + Images - Fried bacon pork ham burgers sausage roast ribs coleslaw BBQ etc., etc., etc.,
Spaced out Engineer
5 / 5 (1) Oct 09, 2015
I could weep. This is amazing. I feel for the pigs, but we are super predators on a mission to comprehend the cosmos. At least their orgasms last 30 mins, but then again I have yet to meet someone whom has left the moment.
antialias_physorg
1 / 5 (1) Oct 09, 2015
I feel for the pigs

I dunno. Better this than sausage. And when we look at the scale of the meat industry vs. this then - if it's a compassion issue - we should probably take up arms against every pig farmer before we even start thinking about opposing this.
EWH
3 / 5 (2) Oct 11, 2015
If you can transplant the pig organs into humans, then you can transplant human organs into pigs - for instance human uteri and ovaries, perhaps even ones grown from stem cells. That would break the monopoly of women on human reproduction, and allow some exciting opportunities for modern mad-scientists. I'm sure somebody will call it "unethical", and almost as sure that the Chinese won't be fazed at all.
Shootist
5 / 5 (1) Oct 11, 2015
Haji is gonna be pissed
antialias_physorg
3.7 / 5 (3) Oct 12, 2015
That would break the monopoly of women on human reproduction

Which they have been exploiting shamelessly, right?
Or do you suggest this would validate people shagging animals? (Well...maybe in the eyes of the church. Abortions being immoral and all that)
EWH
2.3 / 5 (3) Oct 12, 2015
"Which they have been exploiting shamelessly, right?"

Well, maybe being involved in about 25 contested custody cases, including one of a father who couldn't get custody even when the mother straight-up sold the baby, gives me an unusual perspective, but yes, women trade heavily on their reproductive monopoly. The problems with the law and its administration are largely the fault of men letting women get away with financially exploiting men and taking no personal responsibility, but women in general haven't shown the least opposition to being so ridiculously legally privileged.

When women's sexual value to men is greatly reduced by high-quality VR with sexbot attachments and childbearing can be done using actual sows, then women will have little they can do that can't be done with less trouble and risk using technology, and I suspect that their remaining core competencies of consuming, conforming and kvetching will be automated even more easily than poon and pregnancy.
SuperThunder
1 / 5 (3) Oct 16, 2015
This is going to taste awesome!
crusher
not rated yet Oct 27, 2015
There still the minor histocompatibilty problems. Those are proteins like the glucose receptor that are different than human counterparts and that cause resection responses in humans.
That problem cant be solved by gene knockouts.

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